This longitudinal study uses concepts and methods from medical anthropology to contribute to basic research on the course of disorders characterized by medically unexplained somatic symptoms. "Course" is construed as a variable, continuous process involving the mutual interaction of social factors and somatic distress. Chronic fatigue syndrome serves as the case study example. A dichotomized random sample of 80 CFS subjects -- 40 with histories of major depression before the onset of their current illness and 40 with no prior psychiatric histories -- will be drawn from patients meeting criteria for the CDC case definition of chronic fatigue syndrome. Forty subjects who currently meet DSMIII-R criteria for major depression will be identified as a comparison group. Qualitative and quantitative approaches to data collection and analysis are combined in the study design. Greater emphasis is placed, however, upon the qualitative component of the work. Following an initial intake interview, three waves of data will be collected over three years for each subject. Each wave consists of: (a) an ethnographic interview, (b) a semi- structured, open-ended telephone interview, and (c) completion of three questionnaires (twice per wave). An analytical plan is presented to answer each of 4 specific questions that organize the research. (1) What social factors and coping mechanisms are associated with chronic fatigue syndrome? (2) What is the subjective experience and meaning of depressive symptoms and how do symptoms of depression change in relation to somatic symptoms over time? (3) What are the sequential, mutual relations between events and processes in the social world and changes in somatic symptoms? (4) Can specific social processes be identified that serve as "critical transition points" mediating symptomatic change? A number of "qualitative hypotheses" will be examined in the course of the analyses. A typology of the course of disorder that takes social processes into account, and a series of quantitative hypotheses that can be tested in future research will be among the products of the project.